Although diclofenac is an excellent nonsteroidal analgesic anti-inflammatory agent, there is a problem that there are cases where it shows side effects such as gastrointestinal disorders when it is orally administered. For this reason, a variety of topical agents for external use whose effective ingredients are diclofenac have been developed and patches comprising diclofenac sodium have been marketed as drugs for topical analgesic application in Japan.
However, although these patches are characterized by good skin permeability of diclofenac, their application is limited to analgesic, anti-inflammatory use topically. As opposed to conventional preparations for topical application that are commercially available, if it is possible to contain diclofenac at high concentrations stably, to have superior releasability and skin permeability of the drug, and to make the blood concentration of diclofenac in the subjects of administration high at the same levels as those by the aforementioned oral administration or administration with suppositories, effectiveness will possibly be shown against systemic disorders (as analgesic anti-inflammatories, antipyretics or the like). Therefore, the development of such novel patches comprising diclofenac and/or a pharmacologically acceptable salt thereof has been wanted.
In addition, there are many cases where diclofenac comprised in patches that are on the market or are being developed is used in the form of a pharmaceutically acceptable salt, particularly a sodium salt from the standpoints of improving its stability, suppressing reduction in physical properties (intensity, elasticity, durability, adhesiveness, and the like) of the adhesive layers of the patches, decreasing irritation to the skin, etc. However, diclofenac sodium is scarcely soluble in ether but is relatively soluble in water; since its percutaneous absorbability is insufficient, a variety of measures have been taken.
For example, in Japanese Unexamined Patent Application No. Sho 61-280426 (Patent Literature 1), there is described that by using an organic acid such as citric acid in combination with diclofenac sodium to have them comprised in the pressure-sensitive adhesive material layer of an analgesic anti-inflammatory patch, the solubility and skin permeability of diclofenac sodium in the patch are improved. Also, in Japanese Unexamined Patent Application No. Sho 62-181226 (Patent Literature 2), there is described that by using a glycol in addition to an organic acid such as citric acid in combination with diclofenac sodium to have them comprised in the base of an analgesic anti-inflammatory patch, the solubility and skin permeability of diclofenac sodium in the patch are improved. Further, in Japanese Unexamined Patent Application No. 2002-338462 (Patent Literature 3), there is described that by combining and compounding diclofenac sodium, an organic acid such as citric acid, pyrrolidone or a derivative thereof, and an aliphatic acid ester of polyvalent alcohol in the base of an adhesive poultice, diclofenac sodium is stably solubilized in the base to improve the releasability from the poultice and the percutaneous absorbability.